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Sustained ingestion of methadone and the sleep of monkeys
Abstract:
Methadone HCl was administered daily to four stump-tailed macaques. The animals' sleep was periodically examined throughtout a year of methadone maintenance and, in two animals, during eight months of withdrawal. REM sleep was substantially decreased by methadone treatment and gradually returned to predrug values over a 6- to 8-month period of maintenance. Measures of non-REM sleep and awakenings showed similar disruption with no return to predrug values. These changes were not correlated with alterations in plasma-methadone concentrations. REM sleep rebound occurred temporarily upon drug withdrawal in two animals, but no consistent sleep disruption was apparent during the subsequent eight months. Contrary to some suggestions, therefore, tolerance to the sleep-disruptive effects of the drug may be specific and incomplete, and extended REM rebound upon withdrawal is not a universal response.
Insights
Methadone hydrochloride disrupted sleep, significantly reducing REM sleep in macaques. Tolerance to these effects was incomplete, and withdrawal did not consistently cause REM sleep rebound.
Area of Science:
- Neuroscience
- Pharmacology
- Sleep Medicine
Background:
- Opioid medications like methadone hydrochloride are used for pain management and opioid use disorder.
- The effects of chronic methadone administration on sleep architecture, particularly REM sleep, require further elucidation.
- Understanding sleep disruption and withdrawal effects is crucial for patient care and treatment protocols.
Purpose of the Study:
- To investigate the long-term effects of daily methadone hydrochloride administration on sleep patterns in stump-tailed macaques.
- To examine sleep disruption during methadone maintenance and withdrawal phases.
- To assess the development of tolerance to methadone's sleep-disruptive effects and REM sleep rebound phenomena.
Main Methods:
- Daily administration of methadone hydrochloride to four stump-tailed macaques for one year.
- Periodic polysomnographic sleep examinations during maintenance and an eight-month withdrawal period in two animals.
- Analysis of REM sleep, non-REM sleep, and awakenings in relation to plasma methadone concentrations.
Main Results:
- Methadone significantly decreased REM sleep during maintenance, with a gradual return to baseline over 6-8 months.
- Non-REM sleep and awakenings were also disrupted, without recovery during maintenance.
- REM sleep rebound was temporary upon withdrawal; no consistent sleep disruption was observed during the subsequent eight months.
Conclusions:
- Tolerance to methadone's sleep-disruptive effects may be specific and incomplete.
- Extended REM sleep rebound following methadone withdrawal is not a universal response in this model.
- Findings suggest complex and potentially incomplete adaptation to chronic methadone exposure impacting sleep.